Nano-bio interactions of Gum Arabic-stabilized lanthanide-based upconverting nanoparticles: <i>in vitro</i> and <i>in vivo</i> study

Lanthanide-based nanoparticles (Ln-NPs) are highly valued for their unique optical and magnetic properties, making them useful in various scientific fields, including materials science and biomedicine. This study investigated the use of Gum Arabic (GA), a natural, non-toxic biopolymer, as capping agent for Ln-NPs to enhance their biocompatibility and chemical and colloidal stability. Specifically, Er³⁺/Yb³⁺ co-doped NaGdF₄ Ln-NPs were modified with GA, followed by their characterization with respect to upconversion properties and <i>in vitro</i> as well as <i>in vivo</i> toxicity. Herein, widely used ligand-free and polyacrylic acid (PAA)-capped Ln-NPs were used as reference materials. Importantly, the GA-modified Ln-NPs exhibited superior stability in aqueous and biologically relevant media, as well as relatively lower cytotoxicity across multiple cell lines, including U-87 MG, HEPG2, and J774A.1. <i>In vivo</i> studies using zebrafish embryos confirmed the minimal toxicity of GA-capped Ln-NPs. Despite overall low non-specific cellular uptake, hyperspectral imaging and inductively coupled plasma mass spectrometry confirmed the colocalization of the Ln-NPs as a function of their surface chemistry in both cell models and zebrafish. The results suggest GA as an effective surface-stabilizing agent for Ln-NPs, paving the way for future functionalization with targeting agents.